{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T06:58:37Z","timestamp":1791874717018,"version":"4.3.4"},"reference-count":169,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pituitary tumors (PT) are mostly benign, although occasionally they demonstrate aggressive behavior, invasion of surrounding tissues, rapid growth, resistance to conventional treatments, and multiple recurrences. The pathogenesis of PT is still not fully understood, and the factors responsible for its invasiveness, aggressiveness, and potential for metastasis are unknown. RAF\/MEK\/ERK and mTOR signaling are significant pathways in the regulation of cell growth, proliferation, and survival, its importance in tumorigenesis has been highlighted. The aim of our review is to determine the role of the activation of PI3K\/AKT\/mTOR and RAF\/MEK\/ERK pathways in the pathogenesis of pituitary tumors. Additionally, we evaluate their potential in a new therapeutic approach to provide alternative therapies and improved outcomes for patients with aggressive pituitary tumors that do not respond to standard treatment. We perform a systematic literature search using the PubMed, Embase, and Scopus databases (search date was 2012\u20132023). Out of the 529 screened studies, 13 met the inclusion criteria, 7 related to the PI3K\/AKT\/mTOR pathway, and 7 to the RAF\/MEK\/ERK pathway (one study was used in both analyses). Understanding the specific factors involved in PT tumorigenesis provides opportunities for targeted therapies. We also review the possible new targeted therapies and the use of mTOR inhibitors and TKI in PT management. Although the RAF\/MEK\/ERK and PI3K\/AKT\/mTOR pathways play a pivotal role in the complex signaling network along with many interactions, further research is urgently needed to clarify the exact functions and the underlying mechanisms of these signaling pathways in the pathogenesis of pituitary adenomas and their role in its invasiveness and aggressive clinical outcome.<\/jats:p>","DOI":"10.3390\/ijms241310952","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T16:06:37Z","timestamp":1688141197000},"page":"10952","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["The Role of Activation of PI3K\/AKT\/mTOR and RAF\/MEK\/ERK Pathways in Aggressive Pituitary Adenomas\u2014New Potential Therapeutic Approach\u2014A Systematic Review"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0413-2679","authenticated-orcid":false,"given":"Aleksandra","family":"Derwich","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland"},{"name":"Doctoral School, Poznan University of Medical Sciences, 60-812 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Sykutera","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Bromi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1730-0176","authenticated-orcid":false,"given":"B\u0142a\u017cej","family":"Rubi\u015b","sequence":"additional","affiliation":[{"name":"Department of Clinical Chemistry and Molecular Diagnostics, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6296-7220","authenticated-orcid":false,"given":"Marek","family":"Rucha\u0142a","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1510-4702","authenticated-orcid":false,"given":"Nadia","family":"Sawicka-Gutaj","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, 60-355 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s42000-019-00168-8","article-title":"Pituitary Tumors: Epidemiology and Clinical Presentation Spectrum","volume":"19","author":"Berrocal","year":"2020","journal-title":"Hormones"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1002\/cncr.20412","article-title":"The Prevalence of Pituitary Adenomas: A Systematic Review","volume":"101","author":"Ezzat","year":"2004","journal-title":"Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1038\/s41379-021-00820-y","article-title":"Pituitary Neuroendocrine Tumors: A Model for Neuroendocrine Tumor Classification","volume":"34","author":"Asa","year":"2021","journal-title":"Mod. 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